Compounds having an indolobenzoxazine skeleton were disclosed in U.S. Pat. Nos. 4,493,836 and 4,318,910 by Lucien Nedelec et al., and in U.S. Pat. No. 4,238,486 by James H. Jones, in which anti-Parkinson and antihypertensive activity is indicated. In these known compounds, the carbon atom at the la position of the indolobenzoxazine skeleton is unsubstituted.
Pain is a complaint due to physical or mental causes, and man has endeavored, since ancient times, to synthesize drugs capable of eliminating or relieving the pain.
Stimuli causing pain include, among others, chemical, electrical, thermal and mechanical ones. Pain signals given to primary sensory nerves by these stimuli are transmitted to the cerebral cortex through the spinal cord, where the sensation is recorded as pain. In the transmission of pain, various neuropeptides participate. Above all, substance-P (SP) is a peptide consisting of 11 amino acids belonging to tachykinins, which is counted as one of the substances transmitting information from the primary sensory nerve to the dorsal horn of the spinal cord, which participates in, other than pain, central nervous system diseases and inflammatory diseases. Therefore, drugs capable of suppressing the stimuli transmitting the action of SP can be used as excellent analgesics.
As a strong analgesic which has been known best, mention is made of the narcotic analgesics, e.g. morphine, and a number of its related compounds have been synthesized. Most of these drugs, however, cause tolerance and physical and mental dependency, and the strength of such tolerance and dependency is assumed to be in direct proportion to the analgesic activity. Circumstances being such as above, the development of a non-narcotic analgesic which does not act on a morphine-acceptor has been ardently desired.